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Transcriptional and Post‐transcriptional Regulatory Mechanisms Lead to Metabolic Adjustment in Response to Glucose Availability
Author(s) -
Munshi Azad Hossain,
Claggett Julia M,
Johnson Tracy L.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.802.6
Subject(s) - rna splicing , intron , gene isoform , gene , gene expression , transcription factor , transcriptional regulation , rna , regulation of gene expression , alternative splicing , biology , rna binding protein , microbiology and biotechnology , genetics
The transcription factor Gcr1 controls expression of over 75% of the genes in actively growing yeast. Yet, despite its widespread effects, regulation of Gcr1 itself remains poorly understood. Here we show that posttranscriptional Gcr1 regulation is nutrient‐dependent. Moreover, GCR1 RNA contains a highly conserved intron, which allows the cell to generate multiple RNA and protein isoforms whose levels change upon glucose depletion. Intriguingly, an isoform generated by intron retention is exported from the nucleus, and its translation is initiated from a conserved, intronic translation start site. Expression of gene products from both the spliced and unspliced RNAs is essential, as cells expressing only one isoform cannot adjust their metabolic program in response to environmental changes. Finally, we show that the Gcr1 proteins form dimers, providing an elegant mechanism by which this one gene, through its regulation, can perform the repertoire of transcriptional activities necessary for fine‐tuned environmental response. So, this study provides a striking example of how alternative splicing in the form of intron‐retention can present the cell with novel mechanisms for regulating gene expression. Support or Funding Information This work was supported by the National Science Foundation (MCB‐1051921 to T.L.J.) and the National Institute of General Medical Sciences ( GM‐085474 to T.L.J.)